Recruiting
Phase 1

Tocilizumab

Sponsor:

Brian Miller

Code:

NCT02874573

Conditions

Schizophrenia

Psychotic Disorders

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Interventions

Tocilizumab

Normal saline

Study Details

Brief summary:

This study is a Phase 1 clinical trial to determine the safety, tolerability, and efficacy of Tocilizumab (Actemra) as an adjunct to antipsychotic medications in stable outpatients with schizophrenia. Tocilizumab (structural formula C6428H9976N1720O2018S42) is a recombinant humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody of the immunoglobulin G1 (IgG1) subclass. Tocilizumab is formulated as a concentrate for solution for infusion, and will be administered by intravenous infusion.

The investigators propose a 12-week randomized controlled trial of tocilizumab, given in adjunct to antipsychotics, in N=20 stable outpatients with schizophrenia or schizoaffective disorder and evidence of increased inflammation in the peripheral blood (high-sensitivity C-reactive protein \[hsCRP\]>0.5 mg/dL). The investigators hypothesize that adjunctive treatment with tocilizumab will be associated with significant improvement in cognition compared to placebo in patients with schizophrenia, and baseline IL-6 levels are higher in tocilizumab-treated responders versus non-responders, and there will be greater decreases in hsCRP from baseline to week 12 in tocilizumab-versus placebo-treated responders, with response defined as ≥0.5 standard deviation (SD) improvement in cognition. Tocilizumab is administered as an intravenous infusion every 4 weeks. Following a screening evaluation, participants will receive three infusions of siltuximab, one at baseline, another at week 4 of the study, and another at week 8. The investigators will measure changes in cognitive function and symptoms over a 12-week period. Complementing previous positive clinical trials of non-steroidal anti-inflammatory drugs, this would be a "proof-of-concept" study that targeting specific cytokines is a viable treatment for schizophrenia.

Interleukin 6 and its receptor were discovered and cloned at Osaka University, Japan, by Tadamitsu Kishimoto in the 1980s. In 1997, Chugai Pharmaceuticals began the clinical development of tocilizumab for the treatment of rheumatoid arthritis. Clinical studies for Castleman's disease and systemic juvenile idiopathic arthritis started in 2001 and 2002, respectively. Hoffmann-La Roche co-developed the drug due to a license agreement in 2003.

On 11 January 2010, Tocilizumab was approved by the U.S. Food and Drug Administration (US FDA) as Actemra for the treatment of rheumatoid arthritis. The FDA approved tocilizumab for the treatment of systemic juvenile idiopathic arthritis for children from two years of age in April 2011.

Conditions

Schizophrenia

Psychotic Disorders

Study ID

NCT02874573

Start date

Sep, 2016

Status verified date

Jul, 2023

Completion date

Dec 31, 2023

Anticipated

Primary completion date

Dec 31, 2023

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • male and female
  • age 18-55
  • capable of giving informed consent
  • Diagnostic and Statistical Manual of Mental Disorders (DSM)-V diagnosis of schizophrenia or schizoaffective disorder
  • stable based on clinical judgment, no psychiatric hospitalizations in past 3 months, and on the same psychotropic medications for >4 weeks
  • taking a non-clozapine antipsychotic
  • hsCRP >0.3 mg/dL at the screening visit

Exclusion Criteria:

  • imminent danger to self/others
  • antibiotic use in the past 2 weeks
  • current scheduled use of immunomodulatory agents
  • history of an immune disorder
  • illicit drug use in the past 30 days
  • any unstable or untreated medical condition
  • history of gastrointestinal ulcers, diverticulitis, malignancy, CNS demyelinating disorder, seizure disorder, or tuberculosis
  • low absolute neutrophil (<2000) or platelet (<100,000) count
  • abnormal hepatic (AST or ALT >1.5 times the upper limit of normal) or renal (BUN or creatinine>1.5 times the upper limit of normal) function
  • any abnormal lab test result judged to be clinically significant
  • active, chronic or recurrent infections
  • pregnancy
  • breast feeding
  • female and of child-bearing potential who is not using any contraception

Study Design

Enrollment

20 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Treatment Group

Subjects in the tocilizumab group will receive a 4 mg/kg infusion at baseline, and weeks 4 and 8, as per the recommended starting dosing for rheumatoid arthritis

placebo comparator: Control Group

Subjects in the placebo group will receive an infusion of normal saline (with the same packaging and volume as the tocilizumab group) at baseline, and weeks 4 and 8.

Interventions

Tocilizumab

Investigational agent

Normal saline

Placebo

Primary outcome measure

  • Change in Cognition [ Time Frame: Baseline and 12 weeks ]

Central Contacts and Locations

Central contacts

Brian J Miller, MD

706-721-4445brmiller@augusta.edu

Rebecca Nichols, MBA

706-721-4605rnichols@augusta.edu

Locations

Augusta University

Recruiting

Augusta, Georgia, United States, 30912

Contacts

Brian J Miller, MD

706-721-4445brmiller@augusta.edu

Rebecca Nichols, MBA

7067214605rnichols@augusta.edu

More Information

Sponsor

Brian Miller

Last update posted

Jul 21, 2023

Last verified

Jul, 2023

Keywords

  • Inflammation
  • Schizophrenia

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Brian Miller on 2023-07-21.